This invention relates to a method of preparing collagen-containing tissues for use as surgically implantable prostheses such as ligament or tendon replacements and to the protheses made by such a method.
Collagen in the form of fibers represents the most abundant animal protein in mammals; it accounts for over 30% of all proteins. After being manufactured by the cells, the collagen molecules assemble into very characteristic fibrils. These fibrils vary in diameter from tissue to tissue and with the species and age of the animal. In general they range in diameters between 50 and 400 nanometers and are packed into larger bundles which we call fibers. Between these fibrils and fibers lies an interfibrillar material described in the earlier literature as the "ground substance" which we now believe to be composed of a highly organized network of negatively charged polysaccharides and associated polypeptides referred to as proteoglycans. In some structures, such as in tendons, the bundles of collagen fibers are surrounded by a thin connective tissue network which has not been well characterized biochemically. This composite of collagen and proteoglycans is responsible for the structural integrity of the supportive structures of the body such as skin, bone, tendons, blood vessels, etc. Cross-links between the collagen molecules within the fibrils are a prerequisite for these to be able to withstand the physical stresses to which they are subjected. In humans and animals these cross-links are generated by a rather complicated series of intracellular and extracellular events which generate reactive groups on the surface of the collagen molecules. These proceed to form intramolecular and intermolecular cross-links after the molecules assemble in the extracellular space.
Not all the collagen molecules in a given organism are chemically identical. There is great similarity but nevertheless there are various well-defined types of collagen which in some cases are unique to particular tissues. For instance, the collagen in cartilage differs from that of the cornea, tendon, bone matrix, dermis and most other tissues. There are now nine well-defined types of collagen in vertebrates and many new ones are being discovered. Whereas in certain tissues collagen fibrils are considered to be almost permanent, in others such as bone, which undergoes constant remodeling, collagen is constantly being replaced.
One of the earliest chemical modifications of collagen is associated with the process of leather tanning, a technology that has evolved over the ages. During the last 15 years increased interest has developed in the use of collagen and collagen-containing tissues in the manufacturing of medical devices. In some instances, chemical cross-linking with the use of bifunctional reagents such as glutaraldehyde, generates materials which are readily usable (i.e. pericardial patches). In other cases such as when heart valves are manufactured, porcine aortic valves, following chemical treatment, are mounted on frames or stents in order to provide them with a suitable framework. The stents are often covered with a porous material such as woven DACRON.RTM. polyester (DACRON is a trademark of E. I. duPont de Nemours and Company, Wilmington, Del.) to facilitate suturing and tissue ingrowth leading to attachment.
In situations such as tendons and ligaments this type of covering is not very practical because of the magnitude of the forces imposed upon such prostheses. Attaining growth into a DACRON.RTM. polyester sleeve. for instance, which is covering a cross-linked tendon-ligament prosthesis as it traverses the bone will not assure the attachment of the ligament per se. If the prosthesis is partially bio-degradable as is the case of some incompletely cross-linked collagen materials, some degradation of the prosthesis and growth of tissue will occur, but the continued resorption and degradation of the intraarticular portion of the prosthesis will lead to eventual failure.